The nil per os (npo) gene was discovered under the auspices of the applicant's K08 award. It encodes a conserved RNA recognition motif (RRM) protein required for digestive organ development in zebrafish. In the current proposal we wish to extend our studies of this gene into mammals. We have found that NPO is expressed in the mouse embryonic digestive tract and in the crypts of the adult small intestine. Based on these preliminary data and our work in zebrafish, we hypothesize that in mammals NPO is required for intestinal organogenesis and homeostasis. To test this idea we propose to meet the following specific aims: Aim 1: To analyze the spatial and developmental expression patterns of NPO in the mouse embryo and in the adult gastrointestinal tract; Aim 2: To determine the role of NPO in mammalian digestive organ development and homeostasis by conditional gene targeting in the mouse. These studies are intended to provide new insight into the molecular mechanisms of organ development, which ultimately may lead to new treatments for diseases such as organ failure and cancer